Infertility is a problem that afflicts approximately 9% of couples in the United States who wish to have children. The causes of infertility are many and varied. Whatever the cause in the particular case, treatment can be very expensive. Indeed, it is estimated that the annual cost of treating infertile couples in the United States is approximately 1 billion dollars.
Frequently, treatment involves the use of in vitro fertilization (IVF) in which eggs from the woman are recovered and fertilized with the male's sperm. The resulting embryo(s) are then surgically transferred back to the woman's uterus for development to continue. However, only about 25% (at best) of the transplanted embryos implant properly with even fewer resulting in live birth. Failure of transplanted embryos to implant is thus a major difficulty in treating the larger problem of infertility.
One obvious approach to improving the chance of success is to increase the number of embryos being implanted. While the use of multiple embryos (e.g., the transfer of up to four embryos to the uterus at the same time) increases the chances of one of them implanting, the recipient also runs the risk of multiple implants and consequently multiple births. See Elsner et al., Am J Obstet Gynecol 177:350-355 (1997). This method is also unsatisfactory in that if the uterus is physically and chemically unprepared to receive embryos because the hormonal regulation is dysfunctional, simply transplanting more embryos will not solve the problem.
A number of hormones (e.g. estrogen, progesterone, etc.) have been identified as having a role in the preparation of the uterus to receive a transplanted embryo, and thus many attempts to improve implantation frequency have focused on the regulation of these hormones. For example, estrogen appears to play a significant role in regulating uterine receptivity to embryo implantation, and thus one treatment of implantation failure is to regulate (e.g. increase) the estrogen level of the host. This approach to treatment frequently backfires, however, as it is thought that this can cause implantation failure due to improper uterine physiology and chemical receptivity induced by the estrogen treatment. Moreover, increased levels of estrogens employed during IVF treatment have been implicated in severe complications of the Ovarian Hyperstimulation Syndrome (OHS). See e.g. MacDougall et al., Hum Reprod 7:597-600 (1992).
What is needed is an effective substitute for the standard hormonal treatment currently used to increase uterine receptivity to embryo implantation. A one-time, non-invasive direct administration of an estrogen substitute would allow increased use and effectiveness of treatment of implantation failure, without the side effects of increased estrogen levels.